MRR Bioreactor Monitoring

Technology

A sample of the cell culture is pumped from the bioreactor vessel through a closed tube into the MRR device. The MRR device contains one or more magnets that generate a magnetic field across the sample, and a probe assembly connected to a radio system sends a radio-frequency pulse through the sample and detects the return signal to measure the T2 relaxation time of the media. The measured T2 value reflects the properties of the cell culture and can be used to determine the density of cells. To ensure stable and accurate measurements, the MRR device has an insulating enclosure reduces the effects of environmental temperature changes. After measurement, the cell culture sample continues through the recirculation loop and is returned to the bioreactor vessel.  

Problem Addressed

The manufacture of biological therapeutic products such as antibodies and viral vectors is commonly carried out using bioreactor-based cultures of genetically engineered cells. During the operation of a bioreactor, viable cell density is commonly used as a proxy for total biologic productivity, providing insight into bioreactor efficiency and overall success of the ongoing culture. Conventional methods of measuring cell density, such as cell counting techniques or spectroscopy, often involve removing samples from the bioreactor, ultimately destroying the cells in that sample. Regular sampling can be impractical for small research reactors (<2mL), which are widely used for process development. However, using very small sample volumes increases sample-to-sample variability. This invention addresses these limitations by providing an MRR-based cell density measurement device that enables real-time, continuous measurement of cell density without the removal or destruction of cells.  

Advantages

• Relaxometry measurements are performed on the culture media rather than directly on the cells, allowing operation with a smaller static magnetic field than would be required for direct cellular measurements.
• Measurements can be performed continuously and at a much higher frequency than techniques that require physically removing samples from the bioreactor.
• The closed-loop tubing arrangement prevents the measurements from being influenced by the external environment.
• The approach requires smaller and less expensive hardware required compared to spectroscopy or MRI‑based cell density measurements.